title: VEGFR and type-V RTK activation and signaling.
abstract: Vascular endothelial growth factor receptors (VEGFRs) in vertebrates play essential roles in the regulation of angiogenesis and lymphangiogenesis. VEGFRs belong to the receptor-type tyrosine kinase (RTK) supergene family. They consist of a ligand-binding region with seven immunoglobulin (7 Ig) -like domains, a trans-membrane (TM) domain, and a tyrosine kinase (TK) domain with a long kinase insert (KI) (also known as a type-V RTK). Structurally, VEGFRs are distantly related to the members of the M-colony stimulating factor receptor/platelet-derived growth factor receptor (CSFR)/(PDGFR) family, which have five immunoglobulin (5 Ig)-like domains. However, signal transduction in VEGFRs significantly differs from that in M-CSFR/PDGFRs. VEGFR2, the major signal transducer for angiogenesis, preferentially uses the phospholipase Cγ-protein kinase C (PLC-γ-PKC)-MAPK pathway, whereas M-CSFR/PDGFRs use the PI3 kinase-Ras-MAPK pathway for cell proliferation. In phylogenetic development, the VEGFR-like receptor in nonvertebrates appears to be the ancestor of the 7 Ig- and 5 Ig-RTK families because most nonvertebrates have only a single 7 Ig-RTK gene. In mammals, VEGFRs are deeply involved in pathological angiogenesis, including cancer and inflammation. Thus, an efficient inhibitor targeting VEGFRs could be useful in suppressing various diseases.
authors.affiliation: Jobu University, Isesaki, Gunma 372-8588, Japan.
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D010802:Phylogeny; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: C501162:FLT1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3